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Methods in Molecular Biology (Clifton,... 2024Photodynamic therapy (PDT) is an established therapy used for the treatment of cutaneous skin cancers and other non-infective ailments. There has been recent interest in...
Photodynamic therapy (PDT) is an established therapy used for the treatment of cutaneous skin cancers and other non-infective ailments. There has been recent interest in the opportunity to use aPDT (antimicrobial PDT) to treat skin and soft tissue infections. PDT utilizes photosensitizers that infiltrate all cells and "sensitize" them to a given wavelength of light. The photosensitizer is simply highly absorbent to a given wavelength of light and when excited will produce, in the presence of oxygen, damaging oxygen radicals and singlet oxygen. Bacterial cells are comparatively poor at combatting oxidative stress when compared with human cells therefore a degree of selective toxicity can be achieved with aPDT.In this chapter, we outline methodologies for testing aPDT in vitro using standard lab equipment.
Topics: Photosensitizing Agents; Photochemotherapy; Humans; Singlet Oxygen; Anti-Infective Agents
PubMed: 38949700
DOI: 10.1007/978-1-0716-3981-8_6 -
Theranostics 2024: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment....
: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. : We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation , indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. In and analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.
Topics: Animals; Theranostic Nanomedicine; Humans; Optical Imaging; Mice; Tumor Microenvironment; Cell Line, Tumor; Fluorescent Dyes; Photochemotherapy; Neoplasms; Mice, Nude; Surgery, Computer-Assisted
PubMed: 38948059
DOI: 10.7150/thno.95590 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Jun 2024Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep... (Review)
Review
Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep tissue penetration, shows great potential for tumor imaging and therapy. Ⅰ-Ⅲ-Ⅵ quantum dots exhibit high brightness, broad excitation, easily tunable emission wavelength and superior stability, and do not contain highly toxic heavy metal elements such as cadmium or lead. These advantages make Ⅰ-Ⅲ-Ⅵ quantum dots attract widespread attention in biomedical field. This review summarizes the recent advances in the controlled synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots and their applications in tumor imaging and therapy. Firstly, the organic-phase and aqueous-phase synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots as well as the strategies for regulating the near-infrared photoluminescence are briefly introduced; secondly, representative biomedical applications of near-infrared-emitting cadmium-free quantum dots including early diagnosis of tumor, lymphatic imaging, drug delivery, photothermal and photodynamic therapy are emphatically discussed; lastly, perspectives on the future directions of developing quantum dots for biomedical application and the faced challenges are discussed. This paper may provide guidance and reference for further research and clinical translation of cadmium-free quantum dots in tumor diagnosis and treatment.
Topics: Quantum Dots; Humans; Cadmium; Neoplasms; Optical Imaging; Animals; Photochemotherapy; Drug Delivery Systems; Infrared Rays; Spectroscopy, Near-Infrared
PubMed: 38932550
DOI: 10.7507/1001-5515.202404002 -
Nutrients Jun 2024Cancer therapy, from malignant tumor inhibition to cellular eradication treatment, remains a challenge, especially regarding reduced side effects and low energy...
Cancer therapy, from malignant tumor inhibition to cellular eradication treatment, remains a challenge, especially regarding reduced side effects and low energy consumption during treatment. Hence, phytochemicals as cytotoxic sensitizers or photosensitizers deserve special attention. The dark and photo-response of Yemenite 'Etrog' leaf extracts applied to prostate PC3 cancer cells is reported here. An XTT cell viability assay along with light microscope observations revealed pronounced cytotoxic activity of the extract for long exposure times of 72 h upon concentrations of 175 μg/mL and 87.5 μg/mL, while phototoxic effect was obtained even at low concentration of 10.93 μg/mL and a short introduction period of 1.5 h. For the longest time incubation of 72 h and for the highest extract concentration of 175 μg/mL, relative cell survival decreased by up to 60% (below the IC). In combined phyto-photodynamic therapy, a reduction of 63% compared to unirradiated controls was obtained. The concentration of extract in cells versus the accumulation time was inversely related to fluorescence emission intensity readings. Extracellular ROS production was also shown. Based on an ATR-FTIR analysis of the powdered leaves and their liquid ethanolic extract, biochemical fingerprints of both polar and non-polar phyto-constituents were identified, thereby suggesting their implementation as phyto-medicine and phyto-photomedicine.
Topics: Humans; Male; Plant Extracts; Photochemotherapy; Prostatic Neoplasms; Plant Leaves; Cell Survival; Photosensitizing Agents; PC-3 Cells; Reactive Oxygen Species; Yemen; Cell Line, Tumor; Antineoplastic Agents, Phytogenic
PubMed: 38931175
DOI: 10.3390/nu16121820 -
International Journal of Molecular... Jun 2024Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage...
Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound , which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC value of 3.01 µM. A distinct preference for HepG2 cells over HELF cells is observed with conjugate but not with compound . In vivo experiments further confirm that conjugate has a specific affinity for tumor tissues, and the combination treatment of conjugate with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.
Topics: Humans; Photochemotherapy; Animals; Mice; Porphobilinogen; Photosensitizing Agents; Hep G2 Cells; Liver Neoplasms; Erlotinib Hydrochloride; Boron Compounds
PubMed: 38928126
DOI: 10.3390/ijms25126421 -
Journal of Nanobiotechnology Jun 2024As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of...
As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu, 3,3'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.
Topics: Copper; Animals; Carcinoma, Hepatocellular; Photochemotherapy; Liver Neoplasms; Mice; Humans; Photosensitizing Agents; Mice, Inbred BALB C; Cell Line, Tumor; Reactive Oxygen Species; Angiogenesis Inhibitors; Porphyrins; Chlorophyllides; Glutathione; Nanoparticles; Catalysis; Metal Nanoparticles; Drug Liberation; Mice, Nude; Antineoplastic Agents
PubMed: 38926721
DOI: 10.1186/s12951-024-02626-x -
Drug Design, Development and Therapy 2024Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of... (Review)
Review
Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.
Topics: Ferroptosis; Humans; Neoplasms; Antineoplastic Agents; Photochemotherapy; Animals; Small Molecule Libraries
PubMed: 38919962
DOI: 10.2147/DDDT.S472178 -
International Journal of Nanomedicine 2024Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These... (Review)
Review
Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.
Topics: Metal-Organic Frameworks; Humans; Neoplasms; Nanocomposites; Drug Delivery Systems; Animals; Photochemotherapy; Antineoplastic Agents; Nanomedicine
PubMed: 38919774
DOI: 10.2147/IJN.S463144 -
International Journal of Nanomedicine 2024This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This...
PURPOSE
This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
METHODS
Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
RESULTS
The DHTPY-Cu@ZOL exhibited proficient HO scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
CONCLUSION
Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.
Topics: Photochemotherapy; Animals; Methicillin-Resistant Staphylococcus aureus; Copper; Anti-Bacterial Agents; Photosensitizing Agents; Wound Infection; Staphylococcal Infections; Reactive Oxygen Species; Imidazoles; Pyridines; Rats; Wound Healing; Male; Humans; Rats, Sprague-Dawley
PubMed: 38919773
DOI: 10.2147/IJN.S458520 -
Journal of Nanobiotechnology Jun 2024Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of... (Review)
Review
Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.
Topics: Humans; Breast Neoplasms; Female; Nanostructures; Nanoparticles; Animals; Photochemotherapy; Inorganic Chemicals
PubMed: 38918821
DOI: 10.1186/s12951-024-02644-9